The long range objective of this project is the development of a rationale and practical procedures for producing immunogens which stimulate particular classes of immune response. Our approach involves study of the surface activity of antigens and adjuvants by means of two experimental models we developed. The first model will investigate the molecular and cellular basis of the biologic activities of single molecular monolayers of a mycobacterial glycolipid adjuvant, trehalose dimycolate (TDM), on the surface of beads. TDM coated beads induce granulomas and toxic reactions which suppress granuloma formation. The interactions of TDM with the host which produce these reactions take place on the surface of the beads where they are accessible to study. We will prepare beads coated with TDM and a series of analogues and attempt to identify the critical interactions of their surfaces with macrophages and components of the complement and coagulation systems. These studies will parallel studies on the adjuvant activity of the same materials. Studies of the induction and suppression of granulomas by TDM coated beads may yield insights into diverse aspects of the host response to cancer. The second model extends our studies of synthetic surface active adjuvants, Pluronic polyols. One of these materials, L121, enhances antibody synthesis, while a closely-related compound, L101, more effectively stimulates delayed type hypersensitivity (DTH). We will attempt to optimize immunogens composed of these and similar synthetic surface active adjuvants, hydrocarbon vehicles, and chemically modified protein antigens for induction of DTH, IgG1, or IgG2 antibody. Preparations with distinctive biological activities will be investigated with systems developed with TDM-coated beads in order to correlate the cellular and molecular interactions on their surfaces with their particular type of immunogenic activity. By means of these studies, we hope to elucidate some of the factors which influence the production of different types of immune response.